PCSK5_HUMAN
ID PCSK5_HUMAN Reviewed; 1860 AA.
AC Q92824; F5H2G7; Q13527; Q96EP4;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 4.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Proprotein convertase subtilisin/kexin type 5;
DE EC=3.4.21.-;
DE AltName: Full=Proprotein convertase 5;
DE Short=PC5;
DE AltName: Full=Proprotein convertase 6;
DE Short=PC6;
DE Short=hPC6;
DE AltName: Full=Subtilisin/kexin-like protease PC5;
DE Flags: Precursor;
GN Name=PCSK5; Synonyms=PC5, PC6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PC6A), AND ALTERNATIVE SPLICING.
RC TISSUE=T-cell;
RX PubMed=8755538; DOI=10.1073/pnas.93.15.7695;
RA Miranda L., Wolf J., Pichuantes S., Duke R., Franzusoff A.;
RT "Isolation of the human PC6 gene encoding the putative host protease for
RT HIV-1 gp160 processing in CD4+ T lymphocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7695-7700(1996).
RN [2]
RP SEQUENCE REVISION.
RA Franzusoff A., Miranda L., Wolf J., Pichuantes S., Lu Y., Duke R.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PC6A).
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PC6A).
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-913 (ISOFORM PC6A).
RA Reudelhuber T.L.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1166-1860 (ISOFORM PC6B).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP FUNCTION IN PREGNANCY ESTABLISHMENT.
RX PubMed=19764806; DOI=10.1021/pr900381a;
RA Kilpatrick L.M., Stephens A.N., Hardman B.M., Salamonsen L.A., Li Y.,
RA Stanton P.G., Nie G.;
RT "Proteomic identification of caldesmon as a physiological substrate of
RT proprotein convertase 6 in human uterine decidual cells essential for
RT pregnancy establishment.";
RL J. Proteome Res. 8:4983-4992(2009).
RN [10]
RP FUNCTION IN PREGNANCY ESTABLISHMENT.
RX PubMed=20555025; DOI=10.1210/en.2010-0326;
RA Heng S., Paule S., Hardman B., Li Y., Singh H., Rainczuk A., Stephens A.N.,
RA Nie G.;
RT "Posttranslational activation of bone morphogenetic protein 2 is mediated
RT by proprotein convertase 6 during decidualization for pregnancy
RT establishment.";
RL Endocrinology 151:3909-3917(2010).
RN [11]
RP FUNCTION.
RX PubMed=22740495; DOI=10.1093/humrep/des203;
RA Paule S., Aljofan M., Simon C., Rombauts L.J., Nie G.;
RT "Cleavage of endometrial alpha-integrins into their functional forms is
RT mediated by proprotein convertase 5/6.";
RL Hum. Reprod. 27:2766-2774(2012).
CC -!- FUNCTION: Serine endoprotease that processes various proproteins by
CC cleavage at paired basic amino acids, recognizing the RXXX[KR]R
CC consensus motif. Likely functions in the constitutive and regulated
CC secretory pathways. Plays an essential role in pregnancy establishment
CC by proteolytic activation of a number of important factors such as
CC BMP2, CALD1 and alpha-integrins. {ECO:0000269|PubMed:19764806,
CC ECO:0000269|PubMed:20555025, ECO:0000269|PubMed:22740495}.
CC -!- INTERACTION:
CC Q92824; O76003: GLRX3; NbExp=3; IntAct=EBI-751290, EBI-374781;
CC Q92824; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-751290, EBI-10172290;
CC Q92824; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-751290, EBI-10171774;
CC Q92824; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-751290, EBI-739863;
CC Q92824; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-751290, EBI-3958099;
CC Q92824; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-751290, EBI-10245291;
CC Q92824; P50222: MEOX2; NbExp=3; IntAct=EBI-751290, EBI-748397;
CC Q92824; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-751290, EBI-945833;
CC Q92824; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-751290, EBI-1210753;
CC Q92824; O75716: STK16; NbExp=3; IntAct=EBI-751290, EBI-749295;
CC Q92824-2; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-11956269, EBI-10173507;
CC Q92824-2; Q8WW18: C17orf50; NbExp=3; IntAct=EBI-11956269, EBI-12877892;
CC Q92824-2; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-11956269, EBI-7317823;
CC Q92824-2; Q02930-3: CREB5; NbExp=6; IntAct=EBI-11956269, EBI-10192698;
CC Q92824-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11956269, EBI-3867333;
CC Q92824-2; Q8NFT6-2: DBF4B; NbExp=3; IntAct=EBI-11956269, EBI-12205861;
CC Q92824-2; Q92608: DOCK2; NbExp=3; IntAct=EBI-11956269, EBI-448771;
CC Q92824-2; Q9NVL1-2: FAM86C1P; NbExp=3; IntAct=EBI-11956269, EBI-12845222;
CC Q92824-2; O95363: FARS2; NbExp=3; IntAct=EBI-11956269, EBI-2513774;
CC Q92824-2; O43559: FRS3; NbExp=3; IntAct=EBI-11956269, EBI-725515;
CC Q92824-2; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-11956269, EBI-11978177;
CC Q92824-2; P49639: HOXA1; NbExp=5; IntAct=EBI-11956269, EBI-740785;
CC Q92824-2; P17482: HOXB9; NbExp=3; IntAct=EBI-11956269, EBI-745290;
CC Q92824-2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-11956269, EBI-6509505;
CC Q92824-2; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-11956269, EBI-11959885;
CC Q92824-2; P60410: KRTAP10-8; NbExp=6; IntAct=EBI-11956269, EBI-10171774;
CC Q92824-2; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-11956269, EBI-10172052;
CC Q92824-2; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-11956269, EBI-1052037;
CC Q92824-2; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-11956269, EBI-10176379;
CC Q92824-2; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-11956269, EBI-10241252;
CC Q92824-2; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-11956269, EBI-12196745;
CC Q92824-2; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-11956269, EBI-9996449;
CC Q92824-2; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-11956269, EBI-751260;
CC Q92824-2; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-11956269, EBI-3958099;
CC Q92824-2; Q5T752: LCE1D; NbExp=6; IntAct=EBI-11956269, EBI-11741311;
CC Q92824-2; Q5T754: LCE1F; NbExp=3; IntAct=EBI-11956269, EBI-11958008;
CC Q92824-2; Q5TA81: LCE2C; NbExp=6; IntAct=EBI-11956269, EBI-11973993;
CC Q92824-2; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-11956269, EBI-10245291;
CC Q92824-2; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-11956269, EBI-6658837;
CC Q92824-2; Q99750: MDFI; NbExp=3; IntAct=EBI-11956269, EBI-724076;
CC Q92824-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11956269, EBI-16439278;
CC Q92824-2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-11956269, EBI-22310682;
CC Q92824-2; Q6NSM0: NR1D2; NbExp=3; IntAct=EBI-11956269, EBI-10250949;
CC Q92824-2; Q92570: NR4A3; NbExp=3; IntAct=EBI-11956269, EBI-13644623;
CC Q92824-2; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-11956269, EBI-1210753;
CC Q92824-2; P32242: OTX1; NbExp=5; IntAct=EBI-11956269, EBI-740446;
CC Q92824-2; P29122: PCSK6; NbExp=3; IntAct=EBI-11956269, EBI-2683528;
CC Q92824-2; Q9NRQ2: PLSCR4; NbExp=3; IntAct=EBI-11956269, EBI-769257;
CC Q92824-2; Q12837: POU4F2; NbExp=6; IntAct=EBI-11956269, EBI-17236143;
CC Q92824-2; Q9NUL5-4: SHFL; NbExp=3; IntAct=EBI-11956269, EBI-11955083;
CC Q92824-2; P49901: SMCP; NbExp=3; IntAct=EBI-11956269, EBI-750494;
CC Q92824-2; O43609: SPRY1; NbExp=3; IntAct=EBI-11956269, EBI-3866665;
CC Q92824-2; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-11956269, EBI-750487;
CC Q92824-2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-11956269, EBI-11741437;
CC Q92824-2; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-11956269, EBI-3650647;
CC Q92824-2; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-11956269, EBI-492476;
CC Q92824-2; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-11956269, EBI-5235829;
CC Q92824-2; Q15645: TRIP13; NbExp=3; IntAct=EBI-11956269, EBI-358993;
CC Q92824-2; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-11956269, EBI-11975223;
CC Q92824-2; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-11956269, EBI-11957216;
CC Q92824-2; Q8IVP9: ZNF547; NbExp=3; IntAct=EBI-11956269, EBI-12895421;
CC Q92824-2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-11956269, EBI-625509;
CC Q92824-2; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-11956269, EBI-11962574;
CC -!- SUBCELLULAR LOCATION: [Isoform PC6A]: Secreted. Note=Secreted through
CC the regulated secretory pathway. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform PC6B]: Endomembrane system; Single-pass
CC type I membrane protein. Note=Type I membrane protein localized to a
CC paranuclear post-Golgi network compartment in communication with early
CC endosomes. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=PC6B; Synonyms=Long;
CC IsoId=Q92824-1; Sequence=Displayed;
CC Name=PC6A; Synonyms=Short;
CC IsoId=Q92824-2; Sequence=VSP_042017, VSP_042018;
CC -!- TISSUE SPECIFICITY: Expressed in T-lymphocytes.
CC -!- DOMAIN: The propeptide domain acts as an intramolecular chaperone
CC assisting the folding of the zymogen within the endoplasmic reticulum.
CC -!- DOMAIN: AC 1 and AC 2 (clusters of acidic amino acids) contain sorting
CC information. AC 1 directs TGN localization and interacts with the TGN
CC sorting protein PACS-1 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR EMBL; U56387; AAC50643.2; -; mRNA.
DR EMBL; AL834522; CAD39178.1; -; mRNA.
DR EMBL; AL359253; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353607; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391868; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL589653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471089; EAW62575.1; -; Genomic_DNA.
DR EMBL; BC012064; AAH12064.1; -; mRNA.
DR EMBL; U49114; AAA91807.1; -; mRNA.
DR EMBL; AK122718; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS55320.1; -. [Q92824-1]
DR CCDS; CCDS6652.1; -. [Q92824-2]
DR PIR; G02428; G02428.
DR PIR; JC6148; JC6148.
DR RefSeq; NP_001177411.1; NM_001190482.1. [Q92824-1]
DR RefSeq; NP_006191.2; NM_006200.5. [Q92824-2]
DR AlphaFoldDB; Q92824; -.
DR SMR; Q92824; -.
DR BioGRID; 111152; 111.
DR IntAct; Q92824; 79.
DR STRING; 9606.ENSP00000446280; -.
DR BindingDB; Q92824; -.
DR ChEMBL; CHEMBL2826; -.
DR GuidetoPHARMACOLOGY; 2385; -.
DR MEROPS; S08.076; -.
DR GlyGen; Q92824; 12 sites.
DR iPTMnet; Q92824; -.
DR PhosphoSitePlus; Q92824; -.
DR BioMuta; PCSK5; -.
DR DMDM; 357529585; -.
DR MassIVE; Q92824; -.
DR PaxDb; Q92824; -.
DR PeptideAtlas; Q92824; -.
DR PRIDE; Q92824; -.
DR ProteomicsDB; 75502; -. [Q92824-1]
DR ProteomicsDB; 75503; -. [Q92824-2]
DR Antibodypedia; 27199; 205 antibodies from 26 providers.
DR DNASU; 5125; -.
DR Ensembl; ENST00000376752.8; ENSP00000365943.4; ENSG00000099139.14. [Q92824-2]
DR Ensembl; ENST00000545128.5; ENSP00000446280.1; ENSG00000099139.14. [Q92824-1]
DR GeneID; 5125; -.
DR KEGG; hsa:5125; -.
DR UCSC; uc004ajz.5; human. [Q92824-1]
DR CTD; 5125; -.
DR DisGeNET; 5125; -.
DR GeneCards; PCSK5; -.
DR HGNC; HGNC:8747; PCSK5.
DR HPA; ENSG00000099139; Tissue enhanced (brain).
DR MIM; 600488; gene.
DR neXtProt; NX_Q92824; -.
DR OpenTargets; ENSG00000099139; -.
DR PharmGKB; PA33093; -.
DR VEuPathDB; HostDB:ENSG00000099139; -.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000155770; -.
DR HOGENOM; CLU_003159_0_0_1; -.
DR InParanoid; Q92824; -.
DR OrthoDB; 518530at2759; -.
DR PhylomeDB; Q92824; -.
DR TreeFam; TF314277; -.
DR BRENDA; 3.4.21.B26; 2681.
DR PathwayCommons; Q92824; -.
DR Reactome; R-HSA-167060; NGF processing.
DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR SignaLink; Q92824; -.
DR SIGNOR; Q92824; -.
DR BioGRID-ORCS; 5125; 5 hits in 1067 CRISPR screens.
DR ChiTaRS; PCSK5; human.
DR GeneWiki; PCSK5; -.
DR GenomeRNAi; 5125; -.
DR Pharos; Q92824; Tchem.
DR PRO; PR:Q92824; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q92824; protein.
DR Bgee; ENSG00000099139; Expressed in buccal mucosa cell and 190 other tissues.
DR ExpressionAtlas; Q92824; baseline and differential.
DR Genevisible; Q92824; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; EXP:Reactome.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0042277; F:peptide binding; ISS:BHF-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:BHF-UCL.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0140447; P:cytokine precursor processing; ISS:BHF-UCL.
DR GO; GO:0007566; P:embryo implantation; ISS:BHF-UCL.
DR GO; GO:0048566; P:embryonic digestive tract development; IMP:BHF-UCL.
DR GO; GO:0048706; P:embryonic skeletal system development; IMP:BHF-UCL.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0001822; P:kidney development; IMP:BHF-UCL.
DR GO; GO:0035108; P:limb morphogenesis; ISS:BHF-UCL.
DR GO; GO:0043043; P:peptide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0016486; P:peptide hormone processing; IDA:BHF-UCL.
DR GO; GO:0016485; P:protein processing; IDA:BHF-UCL.
DR GO; GO:0051004; P:regulation of lipoprotein lipase activity; TAS:Reactome.
DR GO; GO:0002001; P:renin secretion into blood stream; IEP:BHF-UCL.
DR GO; GO:0030323; P:respiratory tube development; ISS:BHF-UCL.
DR GO; GO:0006465; P:signal peptide processing; IDA:HGNC-UCL.
DR GO; GO:0019058; P:viral life cycle; IEP:BHF-UCL.
DR CDD; cd00064; FU; 16.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 3.30.70.850; -; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR032778; GF_recep_IV.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR034182; Kexin/furin.
DR InterPro; IPR002884; P_dom.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR032815; S8_pro-domain.
DR InterPro; IPR038466; S8_pro-domain_sf.
DR Pfam; PF14843; GF_recep_IV; 1.
DR Pfam; PF01483; P_proprotein; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF16470; S8_pro-domain; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SMART; SM00181; EGF; 16.
DR SMART; SM00261; FU; 22.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR SUPFAM; SSF57184; SSF57184; 7.
DR PROSITE; PS51829; P_HOMO_B; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues; Glycoprotein;
KW Hydrolase; Membrane; Pregnancy; Protease; Reference proteome; Repeat;
KW Secreted; Serine protease; Signal; Transmembrane; Transmembrane helix;
KW Zymogen.
FT SIGNAL 1..32
FT /evidence="ECO:0000250"
FT PROPEP 33..114
FT /evidence="ECO:0000250"
FT /id="PRO_0000027102"
FT CHAIN 115..1860
FT /note="Proprotein convertase subtilisin/kexin type 5"
FT /id="PRO_0000027103"
FT TOPO_DOM 115..1743
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1744..1764
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1765..1860
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 134..453
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 461..601
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT REPEAT 630..680
FT /note="FU 1"
FT REPEAT 683..730
FT /note="FU 2"
FT REPEAT 734..777
FT /note="FU 3"
FT REPEAT 779..824
FT /note="FU 4"
FT REPEAT 832..879
FT /note="FU 5"
FT DOMAIN 869..913
FT /note="PLAC"
FT REPEAT 882..927
FT /note="FU 6"
FT REPEAT 929..979
FT /note="FU 7"
FT REPEAT 982..1028
FT /note="FU 8"
FT REPEAT 1032..1077
FT /note="FU 9"
FT REPEAT 1079..1121
FT /note="FU 10"
FT REPEAT 1125..1168
FT /note="FU 11"
FT REPEAT 1177..1221
FT /note="FU 12"
FT REPEAT 1225..1272
FT /note="FU 13"
FT REPEAT 1274..1318
FT /note="FU 14"
FT REPEAT 1320..1363
FT /note="FU 15"
FT REPEAT 1365..1411
FT /note="FU 16"
FT REPEAT 1415..1461
FT /note="FU 17"
FT REPEAT 1465..1510
FT /note="FU 18"
FT REPEAT 1514..1559
FT /note="FU 19"
FT REPEAT 1563..1610
FT /note="FU 20"
FT REPEAT 1614..1659
FT /note="FU 21"
FT REPEAT 1665..1712
FT /note="FU 22"
FT REGION 636..1727
FT /note="CRM (Cys-rich motif)"
FT REGION 1807..1826
FT /note="AC 1"
FT /evidence="ECO:0000250"
FT REGION 1838..1860
FT /note="AC 2"
FT /evidence="ECO:0000250"
FT MOTIF 519..521
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 171
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 212
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 386
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT SITE 114..115
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 665
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 752
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 802
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 852
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1014
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1685
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1707
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 876..913
FT /note="GEYVDEHGHCQTCEASCAKCQGPTQEDCTTCPMTRIFD -> ATEESWAEGG
FT FCMLVKKNNLCQRKVLQQLCCKTCTFQG (in isoform PC6A)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:8755538,
FT ECO:0000303|Ref.7"
FT /id="VSP_042017"
FT VAR_SEQ 914..1860
FT /note="Missing (in isoform PC6A)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:8755538,
FT ECO:0000303|Ref.7"
FT /id="VSP_042018"
FT CONFLICT 2
FT /note="G -> D (in Ref. 1; AAC50643)"
FT /evidence="ECO:0000305"
FT CONFLICT 4
FT /note="G -> E (in Ref. 1; AAC50643)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="F -> S (in Ref. 1; AAC50643)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="A -> V (in Ref. 1; AAC50643)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="R -> A (in Ref. 7; AAA91807)"
FT /evidence="ECO:0000305"
FT CONFLICT 601
FT /note="Q -> R (in Ref. 1; AAC50643)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1860 AA; 206942 MW; 96B3E7C8215BCC85 CRC64;
MGWGSRCCCP GRLDLLCVLA LLGGCLLPVC RTRVYTNHWA VKIAGGFPEA NRIASKYGFI
NIGQIGALKD YYHFYHSRTI KRSVISSRGT HSFISMEPKV EWIQQQVVKK RTKRDYDFSR
AQSTYFNDPK WPSMWYMHCS DNTHPCQSDM NIEGAWKRGY TGKNIVVTIL DDGIERTHPD
LMQNYDALAS CDVNGNDLDP MPRYDASNEN KHGTRCAGEV AAAANNSHCT VGIAFNAKIG
GVRMLDGDVT DMVEAKSVSF NPQHVHIYSA SWGPDDDGKT VDGPAPLTRQ AFENGVRMGR
RGLGSVFVWA SGNGGRSKDH CSCDGYTNSI YTISISSTAE SGKKPWYLEE CSSTLATTYS
SGESYDKKII TTDLRQRCTD NHTGTSASAP MAAGIIALAL EANPFLTWRD VQHVIVRTSR
AGHLNANDWK TNAAGFKVSH LYGFGLMDAE AMVMEAEKWT TVPRQHVCVE STDRQIKTIR
PNSAVRSIYK ASGCSDNPNR HVNYLEHVVV RITITHPRRG DLAIYLTSPS GTRSQLLANR
LFDHSMEGFK NWEFMTIHCW GERAAGDWVL EVYDTPSQLR NFKTPGKLKE WSLVLYGTSV
QPYSPTNEFP KVERFRYSRV EDPTDDYGTE DYAGPCDPEC SEVGCDGPGP DHCNDCLHYY
YKLKNNTRIC VSSCPPGHYH ADKKRCRKCA PNCESCFGSH GDQCMSCKYG YFLNEETNSC
VTHCPDGSYQ DTKKNLCRKC SENCKTCTEF HNCTECRDGL SLQGSRCSVS CEDGRYFNGQ
DCQPCHRFCA TCAGAGADGC INCTEGYFME DGRCVQSCSI SYYFDHSSEN GYKSCKKCDI
SCLTCNGPGF KNCTSCPSGY LLDLGMCQMG AICKDGEYVD EHGHCQTCEA SCAKCQGPTQ
EDCTTCPMTR IFDDGRCVSN CPSWKFEFEN QCHPCHHTCQ RCQGSGPTHC TSCGADNYGR
EHFLYQGECG DSCPEGHYAT EGNTCLPCPD NCELCHSVHV CTRCMKGYFI APTNHTCQKL
ECGQGEVQDP DYEECVPCEE GCLGCSLDDP GTCTSCAMGY YRFDHHCYKT CPEKTYSEEV
ECKACDSNCG SCDQNGCYWC EEGFFLLGGS CVRKCGPGFY GDQEMGECES CHRACETCTG
PGHDECSSCQ EGLQLLRGMC VHATKTQEEG KFWNDILRKL QPCHSSCKTC NGSATLCTSC
PKGAYLLAQA CVSSCPQGTW PSVRSGSCEN CTEACAICSG ADLCKKCQMQ PGHPLFLHEG
RCYSKCPEGS YAEDGICERC SSPCRTCEGN ATNCHSCEGG HVLHHGVCQE NCPERHVAVK
GVCKHCPEMC QDCIHEKTCK ECTPEFFLHD DMCHQSCPRG FYADSRHCVP CHKDCLECSG
PKADDCELCL ESSWVLYDGL CLEECPAGTY YEKETKECRD CHKSCLTCSS SGTCTTCQKG
LIMNPRGSCM ANEKCSPSEY WDEDAPGCKP CHVKCFHCMG PAEDQCQTCP MNSLLLNTTC
VKDCPEGYYA DEDSNRCAHC HSSCRTCEGR HSRQCHSCRP GWFQLGKECL LQCREGYYAD
NSTGRCERCN RSCKGCQGPR PTDCLSCDRF FFLLRSKGEC HRSCPDHYYV EQSTQTCERC
HPTCDQCKGK GALNCLSCVW SYHLMGGICT SDCLVGEYRV GEGEKFNCEK CHESCMECKG
PGAKNCTLCP ANLVLHMDDS HCLHCCNTSD PPSAQECCDC QDTTDECILR TSKVRPATEH
FKTALFITSS MMLVLLLGAA VVVWKKSRGR VQPAAKAGYE KLADPNKSYS SYKSSYREST
SFEEDQVIEY RDRDYDEDDD DDIVYMGQDG TVYRKFKYGL LDDDDIDELE YDDESYSYYQ
